Ab Initio Study of the Deamination of Formamidine

Abstract

The mechanism for the deamination of formamidine with OH-, H2O, and H3O+ was investigated using computational techniques. Optimized geometries for reactants, intermediates, products, and transition states were determined at the RHF/6-31G(d) and MP2/6-31G(d) levels of theory. Single-point energies were determined at G1 and G2 and using density functional theory (B3LYP) at both optimized geometries and the 6-311G(d,p), 6-311+G(d,p), 6-311++G(d,p) (with OH- only), 6-311G(2df,p), and 6-311+G(3df,2p) basis sets. Frequencies were calculated for all structures studied at both geometries. Intrinsic reaction coordinate analysis was carried out for all transition states. Activation energies were calculated for each pathway investigated. Deamination with H3O+ involves the formation of the same tetrahedral intermediate from the addition of water to either possible protonated formamidine cation followed by a 1,3-proton shift and dissociation to products. Deamination is an unlikely event because of the high activation-energy barrier to the formation of the intermediate (242.4 kJ mol-1 for pathway A and 243.5 kJ mol-1 for pathway B using G2 data). Two pathways for deamination with H2O were studied. Pathway A produced a tetrahedral intermediate by the addition of water followed by a 1,3-proton shift and dissociation to products, and pathway B involved the formation of the tautomer of the formamide product by reaction with water followed by a 1,3-proton shift to yield formamide. Deamination by either pathway is unlikely because of the high activation-energy barriers involved (212.7 kJ mol-1 for the formation of the tetrahedral intermediate of pathway A and 249.2 kJ mol-1 for the formation of the formamide tautomer of pathway B using G2 data). Deamination with OH- yields a tetrahedral intermediate with a much lower activation-energy barrier than for the reaction with H3O+ and H2O (58.2 kJ mol-1 using G2 data), but the deprotonation of formamidine by hydroxide appears to be the most likely process because of the resonance-stabilized deprotonated formamidine anion/water complex formed (ΔE = −163.2 kJ mol-1).